title: CD4+ T cell-mediated granulomatous pathology in schistosomiasis is downregulated by a B cell-dependent mechanism requiring Fc receptor signaling.
abstract: The effector functions of CD4+ T lymphocytes are generally thought to be controlled by distinct populations of regulatory T cells and their soluble products. The role of B cells in the regulation of CD4-dependent host responses is less well understood. Hepatic egg granuloma formation and fibrosis in murine schistosomiasis are dependent on CD4+ lymphocytes, and previous studies have implicated CD8+ T cells or cross-regulatory cytokines produced by T helper (Th) lymphocytes as controlling elements of this pathologic process. In this report, we demonstrate that B cell-deficient (muMT) mice exposed to Schistosoma mansoni develop augmented tissue pathology and, more importantly, fail to undergo the spontaneous downmodulation in disease normally observed during late stages of infection. Unexpectedly, B cell deficiency did not significantly alter T cell proliferative response or cause a shift in the Th1/Th2 balance. Since schistosome-infected Fc receptor-deficient (FcR gamma chain knockout) mice display the same exacerbated egg pathology as that observed in infected muMT mice, the B cell- dependent regulatory mechanism revealed by these experiments appears to require receptor-mediated cell triggering. Together, the data demonstrate that humoral immune response/FcR interactions can play a major role in negatively controlling inflammatory disease induced by CD4+ T cells.
authors.affiliation: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. djankovic@atlas.niaid.nih.gov
authors.forename: D
authors.initials: D
authors.lastname: Jankovic
authors.forename: A W
authors.initials: AW
authors.lastname: Cheever
authors.forename: M C
authors.initials: MC
authors.lastname: Kullberg
authors.forename: T A
authors.initials: TA
authors.lastname: Wynn
authors.forename: G
authors.initials: G
authors.lastname: Yap
authors.forename: P
authors.initials: P
authors.lastname: Caspar
authors.forename: F A
authors.initials: FA
authors.lastname: Lewis
authors.forename: R
authors.initials: R
authors.lastname: Clynes
authors.forename: J V
authors.initials: JV
authors.lastname: Ravetch
authors.forename: A
authors.initials: A
authors.lastname: Sher
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation; D006099:Granuloma / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010063:Ovum / Q000276:immunology; D011961:Receptors, Fc / Q000502:physiology*; D012552:Schistosomiasis / Q000276:immunology / Q000473:pathology*; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D011961:Receptors, Fc